The effect of structural change on the biological activity of a series of imidazothiazoles and thiazolobenzimidazoles is described. It was found that compounds with polar substituents at the 2 or 3 position of the ring system are less acutely toxic while maintaining antiinflammatory activity. Other structural changes, such as the incorporation of a gem-dimethyl substituent in the 6 position, increase acute toxicity and eliminate antiinflammatory activity. The compound with the best activity/toxicity ratio contains an alkyl sulfonyl substituent on the thiazole ring. The thiazolobenzimidazole analogues are more potent than the imidazole analogues.
The antilipidemic properties of diethyl (4balpha,4calpha,9aalpha,4balpha)-3,6-dichlorocyclobutal[1,2-b:3,4-b']bisbenzofuran-9a,9b(4bH,4cH)-dicarboxylate, herein termed dimer 8, were studied in sucrose-fed and in Triton-induced hyperlipidemic rats. Whereas clofibrate (0.4 mmol/kg) exhibited both anticholesterolemic and antitriglyceridemic activity, dimer 8 showed only antitriglyceridemic properties at the lower dose (0.2 mmol/kg) in sucrose-fed rats. Dimer 8 only lowered serum triglycerides levels in Triton WR-1339 hyperlipidemic rats, whereas clofibrate lowered both cholesterol and triglyceride levels. In the chronic sucrose-fed model, dimer 8 and clofibrate lowered hepatic HMG-CoA reducatase activity and produced significant elevations in several parameters of hepatic drug metabolism. No positive relationship between serum cholesterol lowering and reduction of hepatic HMG-CoA reductase activity was observed by these agents in sucrose-fed rats.
Das antihypertensive Pyridazinon (I) wird in die Ester (II) übergeführt, die bei hoher Dosis teilweise eine größere antihypertensive Wirkung besitzen als (I).
Die in situ dargestellten α‐Halogenketone (III) reagieren mit den Mercaptodihydroimidazolen (II) bei Raumtemperatur zu den Hydroxyimidazothiazolen (I) und in siedendem Ethanol zu den Dihydroimidazothiazolen (IV).
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